BEGIN:VCALENDAR VERSION:2.0 PRODID:Icfo X-PUBLISHED-TTL:P1W BEGIN:VEVENT UID:69d4adcb4244f DTSTART:20240715T130000Z SEQUENCE:0 TRANSP:OPAQUE LOCATION:Auditorium and Online (Teams) SUMMARY:ICFO | LI-CHUN LIN CLASS:PUBLIC DESCRIPTION:The locomotion of Caenorhabditis elegans (C. elegans) offers a unique platform for studying complex postures and motor behaviors. In this study\, I investigated locomotor patterns across different ages and genet ic backgrounds of C. elegans\, utilizing customized tracking systems and a dvanced analysis techniques. A comprehensive examination of locomotion beh aviors was conducted using the eigenworm approach. Eigenworms are the prin cipal components of the animals&rsquo\; posture space. I identified specif ic eigenworms associated with forward movement\, turning\, and exaggerated bends. Notably\, spectrin-mutant animals showed a strong correlation betw een their bending movements and a specific eigenworm for turning in wild-t ype animals. These findings suggest that eigenworms offer a universal fram ework to compare different types of worm movement and assess the effects o f mutations. This paves the way for a more informative analysis of worm be havior\, especially when combined with studies of neuronal networks.\nAddi tionally\, I explored the role of proprioception in coordinating motor act ivities within C. elegans\, employing genetic and modeling approaches. The focus of my research was to elucidate the mechanisms underlying proprioce ptive feedback\, including mechanical stress and neuronal signaling\, with a focus on age-related deficits. My findings elucidate that the spectral network associated with a singular proprioceptive DVA interneuron\, which modulates tension and compression states\, serves as a critical determinan t of body posture. Intriguingly\, a striking resemblance was observed betw een animals of early ageing and the mutant animals for &beta\;-spectrin\, where both animals crawled with exaggerated body bends. Moreover\, I show that proprioceptive neurons are found to encode body posture and exhibit a ge-dependent structural and functional alterations\, including protein agg regation and decreased mechanical tension. Notably\, spectrin\, a cytoskel etal component\, emerges as a key player in maintaining proprioceptive int egrity during ageing.\nFurthermore\, I investigated the molecular pathways underlying age-associated proprioceptive defects\, more specifically\, th e role CLP-1 protease in the cleavage of UNC-70/&beta\;-spectrin in ageing animals. Conditional knockout of clp-1 in DVA interneuron revealed altere d locomotor behaviors\, along with the pan-neuronal knockout of clp-1. Giv en the role of spectrin in proprioception through DVA interneuron suggests that clp-1 regulates spectrin in age-related neurodegeneration. Lastly\, I explored the effect of ectopic expression of human &alpha\;&beta\;crysta lline on ageing. We hypothesized that &alpha\;&beta\;-crystallin (HSPB5)\, a small heat shock protein (sHsp)\, will stabilize &beta\;-spectrin and s hield it from clp-1 proteolytic degradation during ageing. I ectopically e xpressed the constitutively active 3E mutant of &alpha\;&beta\;-crystallin pan-neuronally or specifically in DVA. Through locomotion analysis of ani mals from young adult to adult day 6\, I observed a modest rescue in the l ocomotion behavioral pattern in both DVA specific and pan-neuronally expre ssed &alpha\;&beta\;-crystallin animals. We speculate that constitutively active &alpha\;&beta\;-crystallin may bind to proteolytically vulnerable d omains/residues of the UNC-70 protein\, providing protection against prote ases such as clp-1. Collectively\, these findings contribute to our unders tanding of proprioceptive mechanisms in ageing and offer insights into pot ential therapeutic targets for age-related neurodegenerative diseases.\n&n bsp\;\nMonday July 15\, 15:00 h. ICFO Auditorium and Online (Teams)\nThesi s Director: Prof. Dr. Michael Krieg DTSTAMP:20260407T071003Z END:VEVENT END:VCALENDAR